Safety and Efficacy of Rituximab for Treatment of Multicentric Castleman Disease in Malawi

NCT ID: NCT04585893

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-22
• Study Completion Date: 2026-06-07

Brief Summary

The purpose of this study is to determine the safety and efficacy of first-line, risk-stratified Rituximab-based Multicentric Castleman Disease (MCD) treatment in Malawi in a single-arm, phase II clinical trial. This study also aims to compare the cost-effectiveness of first-line Rituximab treatment for MCD in Malawi to chemotherapy.

Detailed Description

This study aims to determine the safety and efficacy of first-line, risk-stratified rituximab-based MCD treatment in Malawi in a single-arm, phase II clinical trial. The investigators will enroll 27 subjects with newly diagnosed or previously treated MCD (who have not previously received rituximab) requiring treatment (B symptoms or hemoglobin <10 g/dL). Subjects will be treated with four weekly doses of rituximab. High-risk subjects (defined as patients with Eastern Cooperative Oncology Group (ECOG) performance status >2 or hemoglobin <8 g/dL) will also receive etoposide chemotherapy. Subjects will be followed for one year for toxicity and two years for survival. The primary outcome will be safety, defined as the frequency of ≥Grade 3 treatment-related Common Terminology Criteria for Adverse Events (AEs). Secondary outcomes will be event-free survival (death, progression, or development of NHL) and 1- and 2-year overall survival (OS). The investigators also aim to compare the cost-effectiveness of first-line rituximab treatment for MCD in Malawi to chemotherapy (using the investigators' historical controls).

Conditions

Multicentric Castleman Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm Rituximab

The safety and efficacy of first-line rituximab will be assessed through a risk-stratified rituximab-based Multicentric Castleman disease (MCD) The planned sample size is 27 adult patients accrued at a rate of 10 patients annually.

High-risk patients (defined as patients with ECOG performance status >2 or hemoglobin <8 g/dL) will receive four weekly doses of rituximab (375 mg/m2) and etoposide (100 mg/m2).

Low-risk patients will receive the same dose of rituximab (four weekly doses at 375 mg/m2) alone.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

375 mg/m\^2 administered via IV infusion weekly for four weeks. Administered via slow IV infusion, starting at 50mg/hr and increasing by 50mg/hr every 30 minutes to a maximum infusion rate of 400mg/hr.

Etoposide

Intervention Type: DRUG

Subjects with high-risk disease will receive 100 mg/m\^2 etoposide weekly for four weeks administered over one hour via IV infusion after completion of rituximab

Interventions

Rituximab

375 mg/m\^2 administered via IV infusion weekly for four weeks. Administered via slow IV infusion, starting at 50mg/hr and increasing by 50mg/hr every 30 minutes to a maximum infusion rate of 400mg/hr.

Intervention Type: DRUG

Etoposide

Subjects with high-risk disease will receive 100 mg/m\^2 etoposide weekly for four weeks administered over one hour via IV infusion after completion of rituximab

Intervention Type: DRUG

Other Intervention Names

Rituxan; Toposar; VP-16

Eligibility Criteria

Inclusion Criteria

1. Newly diagnosed or previously treated subjects with KSHV-associated MCD that is pathologically confirmed by characteristic histologic features and latency-associated nuclear antigen (LANA) positivity by Immunohistochemistry (IHC).

2. Age is greater than or equal 18 years old at time of consent.

3. Can provide informed consent.

4. HIV-infected or HIV-uninfected.

5. If HIV-infected, must be on or willing to start antiretroviral therapy including lamivudine or tenofovir.

6. Willing to comply with study visits.

7. MCD treatment indicated based on the presence of a symptomatic MCD flare, defined as the presence of each of the following three criteria:

1. Fever (subjective or objective)

2. Lymphadenopathy or hepatosplenomegaly

3. At least one of the following signs or symptoms attributable to MCD by the local study investigator:

• Weight loss >5%
• Malaise
• Anemia (Hemoglobin <10 g/dL) within the past 4 weeks
• Thrombocytopenia (Platelets <100 x 103/mL) NOTE: If only two of the three criteria are present, but the provider feels treatment is indicated for a symptomatic MCD flare, this will be allowed after communication with the study principal investigator (PI).

Subjects with low hemoglobin within the past 4 weeks that have since received a blood transfusion are still eligible for participation. The subject's pre-transfusion hemoglobin value will be considered when determining risk classification.

8. Females of childbearing potential must have a negative urine pregnancy test within three days prior to registration.

NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided.

9. Females must agree to abstain from breastfeeding during therapy and for 6 months after the completion of therapy.

10. Females of childbearing potential must be willing to abstain from heterosexual activity or to use two forms of effective methods of contraception from the time of informed consent until 12 months after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, a barrier method plus a hormonal method, or an intrauterine device that meets <1% failure rate for protection from pregnancy in the product label.

11. Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 6 months after the last dose of study therapy.

12. More than 7 days without corticosteroid use prior to starting the treatment.

5. Active infection requiring systemic therapy.

6. Treatment with any investigational drug within 28 days prior to registration.

7. More than 7 days of corticosteroids immediately prior to enrollment. If the subject is taking corticosteroids for more than 7 days, they require a 7 day washout period before enrollment.

8. Bilirubin >3 mg/dL.

9. Creatinine clearance <30 ml/min by Cockcroft-Gault formula.

10. ECOG performance status >3.

11. Pregnant or breastfeeding (Note: Breast milk cannot be stored for future use while the mother is being treated in the study).

Exclusion Criteria

1. Symptomatic, extensive-stage KS (T1 by the AIDS Clinical Trials Group (ACTG) staging system; T1 includes ulceration or edema from KS, raised or non-hard palate oral lesions, or any visceral involvement) requiring urgent treatment, to avoid potential rituximab-induced KS worsening.

2. Previous rituximab use for MCD.

3. Second active malignancy requiring systemic therapy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fogarty International Center of the National Institute of Health

NIH

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew Painschab, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina

Locations

UNC Project, Kamuzu Central Hospital

Lilongwe, , Malawi

Countries

Malawi

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://unclineberger.org/

UNC Lineberger Comprehensive Cancer Center Website Homepage

Other Identifiers

K01TW011470

Identifier Type: NIH

Identifier Source: secondary_id

View Link

LCCC 1950

Identifier Type: -

Identifier Source: org_study_id